Lets take a logical approach here, I have worked with a number of MES systems in the past the most recent being the offering from Camstar their Insite product.
In terms of upgrading my first port of call would be to ask the vendor for the upgrade listing that they should have detailing the new features, bug fixes, GUI differences etc that they give to their client before the upgrade takes place.
With access to this list I would then pool all interested parties together and flesh out how each upgrade feature affects the original install. Its important to have SME’s present that understand the nature of the upgrade and the effect it might have on the previous install.
I would create a document that contains each upgrade feature and state on this document what will be testable as par tog the revalidation process and what it not going to be testable.
This is an important point……for the items that are not testable I would generate a risk assessment and document why these items are not being tested.
This should be a good starting point, if you need any further assistance feel free to contact me directly to discuss.